MOVIPREP, powder for oral solution

Moviprep is indicated in adults for bowel cleansing prior to any clinical procedures requiring a clean bowel e.g. bowel endoscopy or radiology.

Posology

Adults and Older People

A course of treatment consists of two litres of Moviprep. It is strongly recommended that one litre of clear liquid, which may include water, clear soup, fruit juice without pulp, soft drinks, tea and/or coffee without milk, is also taken during the course of treatment.

A litre of Moviprep consists of one 'sachet A' and one 'sachet B' dissolved together in water to make one litre of solution. The reconstituted solution should be drunk over a period of one to two hours. This process should be repeated with a second litre of Moviprep to complete this course.

This course of treatment can be taken either as divided or as single doses and timing is dependent on whether the clinical procedure is conducted with or without general anaesthesia as specified below:

For procedures conducted under general anaesthesia:

1. Divided doses: one litre of Moviprep in the evening before and one litre of Moviprep in the early morning of the day of the clinical procedure. Ensure consumption of Moviprep as well as any other clear fluids has finished at least two hours before the start of the clinical procedure.

2. Single dose: two litres of Moviprep in the evening before the clinical procedure or two litres of Moviprep in the morning of the clinical procedure. Ensure consumption of Moviprep as well as any other clear fluids has finished at least two hours before the start of the clinical procedure.

For procedures conducted without general anaesthesia:

1. Divided doses: one litre of Moviprep in the evening before and one litre of Moviprep in the early morning of the day of the clinical procedure. Ensure consumption of Moviprep as well as any other clear fluids has finished at least one hour before the start of the clinical procedure.

2. Single dose: two litres of Moviprep in the evening before the clinical procedure or two litres of Moviprep in the morning of the clinical procedure. Ensure consumption of Moviprep has finished at least two hours before the start of the clinical procedure. Ensure consumption of any clear fluids has finished at least one hour before the clinical procedure.

Patients should be advised to allow for appropriate time to travel to the colonoscopy unit.

No solid food should be taken from the start of the course of treatment until after the clinical procedure.

Paediatric population

Not recommended for use in children below 18 years of age, as Moviprep has not been studied in the paediatric population.

Method of administration

The route of administration is oral use. A litre of Moviprep consists of one sachet A and one sachet B dissolved together in water to make a one litre solution.

Precautions to be taken before handling or administering the medicinal product.

For instructions on reconstitution of the medicinal product before administration, see section 6.6.

Do not use in patients with known or suspected:

- hypersensitivity to the active substances or to any of the excipients listed in section 6.1

- gastrointestinal obstruction or perforation

- disorders of gastric emptying (e.g. gastroparesis)

- ileus

- phenylketonuria (due to presence of aspartame)

- glucose-6-phosphate dehydrogenase deficiency (due to presence of ascorbate)

- toxic megacolon, which complicates very severe inflammatory conditions of the intestinal tract including Crohn's disease and ulcerative colitis.

Do not use in unconscious patients

Diarrhoea is an expected effect resulting from the use of Moviprep.

Moviprep should be administered with caution to fragile patients in poor health or patients with serious clinical impairment such as:

- impaired gag reflex, or with a tendency to aspiration or regurgitation

- impaired consciousness

- severe renal insufficiency (creatinine clearance <30 mL/min)

- cardiac impairment (NYHA grade III or IV)

- those at risk of arrhythmia, for example those on treatment for cardiovascular disease or who have thyroid disease

- dehydration

- severe acute inflammatory bowel disease

The presence of dehydration should be corrected before the use of Moviprep.

The fluid content of Moviprep when re-constituted with water does not replace regular fluid intake and adequate fluid intake must be maintained.

Semi-conscious patients or patients prone to aspiration or regurgitation should be closely observed during administration, especially if this is via a nasogastric route.

In patients with swallowing problems, who need the addition of a thickener to solutions to enhance an appropriate intake, interactions should be considered, see section 4.5.

If patients develop any symptoms indicating arrhythmia or shifts of fluid/electrolytes (e.g. oedema, shortness of breath, increasing fatigue, cardiac failure), plasma electrolytes should be measured, ECG monitored and any abnormality treated appropriately.

In debilitated fragile patients, patients with poor health, those with clinically significant renal impairment, arrhythmia and those at risk of electrolyte imbalance, the physician should consider performing a baseline and post-treatment electrolyte, renal function test and ECG as appropriate.

Cases of seizures associated with use of macrogol 3350 with electrolytes for bowel preparation were observed in patients either with or without prior history of seizures. These cases were mostly associated with electrolyte abnormalities such as severe hyponatraemia (see section 4.8). Use caution when prescribing macrogol 3350 with electrolytes in patients with a history of seizures, at increased risk of seizure or at risk of electrolyte disturbance. In case of neurologic symptoms, fluid and electrolyte abnormalities should be corrected.

There have been rare reports of serious arrhythmias including atrial fibrillation associated with the use of ionic osmotic laxatives for bowel preparation. These occur predominantly in patients with underlying cardiac risk factors and electrolyte disturbance.

If patients experience symptoms such as severe bloating, abdominal distention, abdominal pain or any other reaction which makes it difficult to continue the preparation, they may slow down or temporarily stop consuming Moviprep and should consult their doctor.

Ischaemic colitis

Post-marketing cases of ischaemic colitis, including serious, have been reported in patients treated with macrogol for bowel preparation. Macrogol should be used with caution in patients with known risk factors for ischaemic colitis or in case of concomitant use of stimulant laxatives (such as bisacodyl or sodium picosulfate). Patients presenting with sudden abdominal pain, rectal bleeding or other symptoms of ischaemic colitis should be evaluated promptly.

Cases of oesophageal rupture (Boerhaave syndrome) associated with excessive vomiting after intake (see section 4.8) of macrogol 3350 with electrolytes for bowel preparation has been reported post-marketing, mostly in elderly patients. Advise patients to stop administration and seek immediate medical assistance if they experience incoercible vomiting and subsequent chest, neck, and abdominal pain, dysphagia, hematemesis or dyspnoea.

This medicinal product contains 363.2 mmol (8.4 g) sodium per course of treatment equivalent to 420% of the of the WHO recommended maximum daily intake of 2 g sodium for an adult. (A course of treatment consists of two litres of Moviprep). To be taken into consideration by patients on a controlled sodium diet. Only a proportion (up to 112.4 mmol (2.6 g) per course treatment) of sodium is absorbed.

This medicinal product contains 28.4 mmol (1.1 g) potassium per course of treatment. (A course of treatment consists of two litres of Moviprep). To be taken into consideration by patients with reduced kidney function or patients on a controlled potassium diet.

The medicinal product contains aspartame, which is a source of phenylalanine. This may be harmful for people with phenylketonuria.

The interaction of Moviprep with other medicinal products has not been studied. Theoretically, medicinal products taken orally (e.g. oral contraceptive pill) one hour before, during and one hour after Moviprep administration may be flushed from the gastrointestinal tract unabsorbed. The therapeutic effect of drugs with a narrow therapeutic index or short half-life may be particularly affected.

Moviprep may result in a potential interactive effect if used with starch-based food thickeners. The Macrogol ingredient counteracts the thickening effect of starch, effectively liquefying preparations that need to remain thick for people with swallowing problems.

Pregnancy

There are no data on the use of Moviprep during pregnancy.

The preparation should only be used during pregnancy if considered essential by the physician.

Breastfeeding

There are no data on the use of Moviprep during lactation.

The preparation should only be used during lactation if considered essential by the physician.

Fertility

There are no data on the effects of Moviprep on fertility.

Moviprep has no influence on the ability to drive and use machines.

Diarrhoea is an expected outcome of bowel preparation. Due to the nature of the intervention, undesirable effects occur in the majority of patients during the process of bowel preparation. Whilst these vary between preparations, nausea, vomiting, bloating, abdominal pain, anal irritation and sleep disturbance commonly occur in patients undergoing bowel preparation. Dehydration may occur as a result of diarrhoea and/or vomiting.

As with other macrogol containing products, allergic reactions including rash, urticaria, pruritus, dyspnoea, angioedema and anaphylaxis are a possibility.

Data from clinical studies are available in a population of 825 patients treated with Moviprep in which undesirable effect data were actively elicited. Additionally, adverse events reported in post marketing are included.

The frequency of adverse reactions to Moviprep is defined using the following convention:

Very common (≥ 1/10)

Common (≥ 1/100 to < 1/10)

Uncommon (≥1/1,000 to < 1/100)

Rare (≥ 1/10,000 to < 1/1,000)

Very rare (< 1/10,000)

Not known (cannot be estimated from the available data)

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple Store.

In case of gross accidental overdosage, where diarrhoea is severe, conservative measures are usually sufficient; generous amounts of fluid, especially fruit juices, should be given. In the rare event of overdose provoking severe metabolic derangement, intravenous rehydration may be used.

Pharmacotherapeutic group: Osmotically acting laxative.

ATC code: A06A D

The oral administration of macrogol-based electrolyte solutions causes moderate diarrhoea and results in rapid emptying of the colon.

Macrogol 3350, sodium sulfate and high doses of ascorbic acid exert an osmotic action in the gut, which induce a laxative effect.

Macrogol 3350 increases the stool volume, which triggers colon motility via neuromuscular pathways.

The physiological consequence is a propulsive colonic transportation of the softened stools. The electrolytes present in the formulation and the supplementary clear liquid intake are included to prevent clinically significant variations of sodium, potassium or water, and thus reduce dehydration risk.

Macrogol 3350 is unchanged along the gut. It is virtually unabsorbed from the gastro- intestinal tract. Any macrogol 3350 that is absorbed is excreted via the urine.

Ascorbic acid is absorbed mainly at the small intestine level by a mechanism of active transport, which is sodium dependant and saturable. There is an inverse relationship between the ingested dose and the percentage of the absorbed dose. For oral doses between 30 and 180 mg an amount of about 70-85% of the dose is absorbed. Following oral intake of up to 12 g ascorbic acid, it is known that only 2 g is absorbed.

After high oral doses of ascorbic acid and when plasma concentrations exceed 14 mg/litre, the absorbed ascorbic acid is mainly eliminated unchanged in the urine.

Preclinical studies provide evidence that macrogol 3350, ascorbic acid and sodium sulfate have no significant systemic toxicity potential, based on conventional studies of pharmacology, repeated dose toxicity, genotoxicity and carcinogenicity.

No studies have been carried out on the genotoxicity, carcinogenicity or toxic effect on reproduction with this product.

In reproductive toxicity studies with macrogol 3350 + electrolytes there were no direct embryotoxic or teratogenic effects in rats even at maternally toxic levels that are a multiple of 14x the maximum recommended dose of Moviprep in humans. Indirect embryofetal effects, including reduction in fetal and placental weights, reduced fetal viability, increased limb and paw hyperflexion and abortions, were noted in the rabbit at a maternally toxic dose that are 0.7 fold of the maximum recommended dose of Moviprep in humans. Rabbits are a sensitive animal test species to the effects of GI-acting substances and the studies were conducted under exaggerated conditions with high dose volumes administered, which are not clinically relevant. The findings may have been a consequence of an indirect effect of macrogol 3350 + electrolytes related to poor maternal condition as the result of an exaggerated pharmacodynamic response in the rabbit. There was no indication of a teratogenic effect.

Aspartame (E951)

Acesulfame Potassium (E950)

Lemon flavour containing maltodextrin, citral, lemon oil, lime oil, arabic gum, vitamin E.

Not applicable

Sachets: Store below 25ºC

Reconstituted Solution: Store below 25ºC. The solution may be refrigerated. Keep the solution covered.

A paper / low density polyethylene / aluminium / low density polyethylene sachet containing 112 g of powder ('sachet A') and a paper / low density polyethylene / aluminium / low density polyethylene sachet containing 11 g of powder ('sachet B'). Both sachets are contained in a transparent bag. One pack of Moviprep contains a single treatment of two bags.

Pack sizes of 1, 10, 40, 80, 160 and 320 packs of a single treatment. Hospital packs of 40 single treatments. Not all pack sizes may be marketed.

Reconstitution of Moviprep in water may take up to 5 minutes and is best performed by adding the powder to the mixing vessel first followed by the water. The patient should wait until all the powder has dissolved before drinking the solution.

After reconstitution in water Moviprep consumption may begin immediately or if preferred it may be cooled before use.